Cited 2 times since 2025 (3.9 per year) source: EuropePMC Lupus science & medicine, Volume 12, Issue 1, 12 2 2025, Pages e001424 Long-term safety and efficacy of the combination of belimumab and rituximab in the treatment of severe and refractory SLE: a preliminary report. van Schaik M, Arends EJ, Wetzels MJAL, Kraaij T, Verbruggen SH, van der Kooij SW, Kamerling SWA, Huizinga T, Goekoop RJ, van Kooten C, Rabelink T, Teng YKO
Objective
Combination therapy with rituximab and belimumab is a novel treatment strategy for severe SLE and lupus nephritis. Phase II studies have shown promising results, although long-term data are currently lacking. To address this, we analysed outcomes of patients with severe treatment-refractory SLE who previously participated in the phase II Synbiose Study, with a particular focus on immunological parameters.
Methods
Eight patients continued belimumab treatment beyond the 2-year duration of the original trial. We conducted a descriptive study to evaluate the course of treatment and immunological parameters over an extended follow-up. Our analyses include blood cell counts, immunoglobulins, autoantibodies, complement markers and clinical disease activity parameters. Additionally, we examined long-term effects on the B cell compartment employing high-sensitivity flow cytometry.
Results
Over a median follow-up period of 6.8 years, six out of eight previously treatment-refractory patients maintained long-term clinical remission, while two experienced a major flare. Among those in remission, two patients achieved immunosuppression-free remission, and four continued belimumab. Long-term effects on humoral (auto-)immunity were a persistent decrease in IgM levels, while IgG normalised. Most patients maintained low autoantibody titres, and complement markers remained normal. On the cellular level, belimumab treatment after rituximab prevented B cell repopulation. Notably, patients exhibited a stable reduction of double-negative (DN) B cells, irrespective of continuing or stopping belimumab.
Conclusions
Long-lasting remission was observed in patients with SLE following combination treatment with rituximab and belimumab. We observed no significant hypogammaglobulinaemia and, notably, persistent reduction of DN B cells.
